Immunization

• Annual Influenza (flu) vaccination is recommended for all persons aged 65 and older and persons in selected high-risk groups.
• Pneumococcal vaccine is recommended for all immunocompetent individuals who are age 65 years and older or otherwise at increased risk for pneumococcal disease. There is insufficient evidence to recommend for or against pneumococcal vaccine for high-risk immunocompromised individuals, but recommendations for vaccinating these persons may be made on other grounds.
• The series of combined tetanus-diphtheria toxoids (Td) should be completed for adults who have not received the primary series, and all adults should receive periodic Td boosters.
• Vaccination against measles and mumps should be provided to all adults born after 1956 who lack evidence of immunity. A second measles vaccination is recommended for adolescents and young adults in settings where such individuals congregate (e.g., high schools and colleges).
• Hepatitis B vaccine is recommended for all young adults not previously immunized and for all persons at high risk for infection (see Clinical Intervention). Hepatitis A vaccine is recommended for persons at high risk for hepatitis A virus (HAV) infection (see Clinical Intervention).
• Varicella vaccine is recommended for susceptible adults, including women of childbearing age not previously infected or vaccinated.

Influenza Vaccine

Inactivated (killed-virus) influenza vaccine containing antigens identical or similar to currently circulating influenza A and B viruses has been shown in controlled trials to be 70-80% effective in preventing influenza illness or reducing severity of influenza illness in healthy children, adolescents, and adults under age 65.1-5 The vaccine has also been reported to reduce clinical symptoms in health care workers,6 which may translate into a reduction in transmission to high-risk patients.

Influenza vaccine should be administered annually to all persons ages 65 and older and to persons 6 months of age or older who are residents of chronic care facilities or suffer from chronic cardiopulmonary disorders, metabolic diseases (including diabetes mellitus), hemoglobinopathies, immunosuppression, or renal dysfunction (“B” recommendation). Influenza vaccine is also recommended for health care providers for high-risk patients (“B” recommendation). In persons at high risk for influenza A (e.g., during institutional outbreaks), amantadine or rimantadine prophylaxis (200 mg/day orally) may be started at the time of vaccination and continued for 2 weeks (“B” recommendation). A lower dose (less than or equal to 100 mg/day) of amantadine is recommended for persons with reduced creatinine clearance and those 65 years of age and older. A reduced dosage (100 mg/day) of rimantadine is indicated for those with reduced renal or hepatic function and for elderly nursing home residents and may also be necessary in healthy persons 65 years and older who experience side effects. Amantadine and rimantadine are most useful as short-term prophylaxis for high-risk persons who have not yet received the vaccine or are vaccinated after influenza A activity in the community has already begun; when the vaccine may be ineffective due to major antigenic changes in the virus; for unimmunized persons who provide care for high-risk persons; to supplement protection provided by vaccine in persons who are expected to have a poor antibody response; and for high-risk persons in whom the vaccine is contraindicated (i.e., those with anaphylactic hypersensitivity to egg protein). If vaccine is contraindicated, amantadine or rimantadine should be started at the beginning of the influenza season and continued daily for the duration of influenza activity in the community.

Pneumococcal Vaccine

Trials in relatively healthy institutionalized elderly (greater than or equal to 50-55 years of age) have demonstrated significant reductions in the incidence of pneumonia and in mortality.9 Other trials of the vaccines in high-risk populations, all adequately designed and conducted, have been unable to detect significant reductions in pneumococcal or all-cause pneumonia or mortality.10 A meta-analysis combining five trials in high-risk populations also reported no effects of vaccine on pneumococcal pneumonia, all-cause pneumonia, or mortality.8 The sample sizes were much smaller than for the analyses in low-risk populations, but effect estimates for most outcomes did not suggest important benefits.

There is little evidence of serious adverse effects from this vaccine, although erythema, induration, or pain at the injection site occur in about one third to one half of patients. Fever, myalgia, and severe reactions occur in no more than 1% of patients.7 Most evidence indicates little difference in adverse reactions to revaccination compared to initial vaccination.

Pneumococcal vaccine is recommended for all immunocompetent individuals who are aged 65 years and older or otherwise at increased risk for pneumococcal disease (“B” recommendation). High-risk groups include institutionalized persons greater than or equal to 50 years of age, persons greater than or equal to 2 years of age with certain medical conditions, including chronic cardiac or pulmonary disease, diabetes mellitus, and anatomic asplenia (excluding sickle cell disease), and persons greater than or equal to 2 years of age who live in special environments or social settings with an identified increased risk of pneumococcal disease (e.g., certain Native American and Alaska Native populations). Routine revaccination is not recommended, but it may be appropriate to consider revaccination in immunocompetent individuals at highest risk for morbidity and mortality from pneumococcal disease (e.g., persons greater than or equal to 75 years of age or with severe chronic disease) who were vaccinated more than 5 years previously. Revaccination with the 23-valent vaccine may be appropriate for high-risk persons who previously received the 14-valent vaccine. There is insufficient evidence to recommend for or against pneumococcal vaccine as an efficacious vaccine for immunocompromised individuals, but recommendations for vaccinating these persons may be made on other grounds, including high incidence and case-fatality rates of pneumococcal disease and minimal adverse effects from the vaccine (“C” recommendation). Immunocompromised conditions associated with high risk for pneumococcal disease include alcoholism, cirrhosis, chronic renal failure, ne-phrotic syndrome, sickle cell disease, multiple myeloma, metastatic or hematologic malignancy, acquired or congenital immunodeficiency (including HIV infection), and other conditions associated with immunosuppression, such as organ transplant. It may be appropriate to consider periodic revaccination in these high-risk immunocompromised patients, who are likely to have poor initial antibody response and rapid decline of antibodies after vaccination.

Tetanus and Diphtheria Vaccine

The efficacy of the tetanus and diphtheria toxoids is established on the basis of clinical studies and decades of experience with universal childhood immunization.12 A primary series of three doses of Td, followed by a booster dose, is highly effective in producing protective antibody titers lasting as long as 15-25 years and results in anamnestic responses with booster immunization as much as 20-30 years later.13 In Sweden, a five-dose regimen (primary series plus boosters at age 8-10 and 18 years) resulted in greater than 90% of subjects having protective tetanus antitoxin levels at age 50 years, slightly fewer than at age 30. Tetanus is unlikely in Americans who have received a primary vaccination series, although clinical immunity may wane somewhat after 10-20 years.11 Td often produces mild local inflammation, occasionally Arthus-type reactions and peripheral neuropathy (following frequent boosters), and rarely, anaphylaxis.

The Td vaccine series should be completed for patients who have not received the primary series, and all adults should receive periodic Td boosters (“A” recommendation). For persons not previously immunized, the recommended schedule for the primary Td series is 0, 2, and 8-14 months. The optimal interval for booster doses is not established. The standard regimen is to provide a Td booster at least once every 10 years, but in the U.S., intervals of 15-30 years between boosters are likely to be adequate in persons who received a complete five-dose series in. For international travelers, an interval of 10 years between boosters is recommended.

Measles, Mumps, and Rubella (MMR) Vaccine

A single dose of measles vaccine is 95% effective in producing long-term immunity.15,16 Seropositivity rates remain high at least 10-15 years following vaccination. Adult infections occur primarily in persons who have not been naturally infected or appropriately vaccinated in the past,14 as well as those who were vaccinated before age 15 months. Revaccinating young adults in settings such as schools and colleges may be effective in reducing the incidence in adults. As with measles, persons born before 1957 can generally be considered immune to mumps and need not be vaccinated. Adverse effects of measles or combined measles-mumps-rubella (MMR) vaccine in adults are usually mild and self-limited.17

MMR vaccine should be administered to all persons born after 1956 who lack evidence of immunity to measles (receipt of live vaccine on or after the first birthday, laboratory evidence of immunity, or a history of physician-diagnosed measles) (“A” recommendation). A second measles vaccination is recommended for adolescents and young adults in settings where such individuals congregate (e.g., high schools, technical schools, and colleges), if they have not previously received a second dose (“B” recommendation). The combined MMR vaccine is preferable to monovalent measles vaccine, since many recipients may also be susceptible to mumps or rubella due to inadequate vaccination or primary vaccine failure. Susceptible individuals should be vaccinated against mumps (“B” recommendation). Administration of the MMR or measles vaccine during pregnancy is not recommended.

Hepatitis B Vaccine

Plasma-derived hepatitis B vaccine, which became available in 1982, has 85-95% protective efficacy when administered in three intramuscular doses to immunocompetent patients.18 Injection into the buttocks has been associated with a suboptimal immune response, and therefore the deltoid muscle is the preferred injection site.20 Local soreness at the injection site is a common side effect.19

Hepatitis B vaccine is recommended for all young adults not previously immunized (“A” recommendation). Hepatitis B vaccine is also recommended for susceptible adults in high-risk groups, including men who have sex with men, injection drug users and their sex partners, persons who have a history of sexual activity with multiple partners in the previous 6 months or have recently acquired another sexually transmitted disease, international travelers to countries where HBV is of high or intermediate endemicity, recipients of certain blood products (including hemodialysis patients), and persons in health-related jobs with frequent exposure to blood or blood products (“A” recommendation). The recommended regimen for the recombinant hepatitis B vaccine is to administer 10 or 20 mcg (depending on vaccine product) intramuscularly in the deltoid muscle at the current visit and at 1 and 6 months later. Clinicians should consider testing antibody response to the vaccine in individuals at very high risk from hepatitis B who are likely to have an inadequate antibody response (i.e., chronic renal dialysis patients, injection drug users, HIV-infected patients).

Hepatitis A Vaccine

Hepatitis A vaccine is recommended for all high-risk adults (“B” recommendation). High-risk groups include persons living in, traveling to, or working in areas where the disease is endemic and periodic hepatitis A outbreaks occur (e.g., Alaska Native, Pacific Islander, and Native American communities, certain religious communities, countries with high or intermediate endemicity), men who have sex with men, users of injection or street drugs (depending on local epidemiology), military personnel, and certain hospital and laboratory workers. Hepatitis A vaccine may also be considered for institutionalized persons (e.g., in prisons and institutions for the developmentally disabled) and workers in these institutions and in day care centers. Where tracking or identification of high-risk patients is not practical or cost-effective, universal vaccination may be a reasonable policy given the minimal adverse consequences of the vaccine. At this writing, the only licensed hepatitis A vaccine is Havrix® (SmithKline Beecham Pharmaceuticals). Two doses (1,440 ELISA units/dose) at 0 and 6-12 months are recommended for persons over age 18 years. The need for periodic booster doses of the vaccine has not been established. For persons requiring immediate protection against hepatitis A (e.g., travelers to high-risk areas who have not previously been vaccinated), clinicians may wish to consider giving IG simultaneously with the first dose of hepatitis A vaccine, although the clinical efficacy of this approach has not been established. IG can also be recommended as an efficacious intervention for short-term (less than or equal to 5-6 months) preexposure prophylaxis against hepatitis A. While some evidence suggests that the vaccine may be more efficacious than IG, the clinical efficacies of these two interventions have not been directly compared. Other factors to consider in choosing between these two interventions include patient preference, the likely duration of exposure, the need for immediate vs. long-term protection, and cost.

Varicella Vaccine

Two doses of varicella vaccine delivered 4-8 weeks apart are recommended for healthy adults with no history of varicella infection or previous vaccination (“B” recommendation). Vaccination efforts should be targeted to susceptible health care workers and family contacts of immunocompromised individuals, and may also be targeted to susceptible adults who live or work in environments with a high likelihood of varicella transmission (e.g., day care centers, residential institutions, colleges, military bases). Given the high prevalence of immunity in adults with no history of chickenpox and the results of cost-effectiveness analysis, clinicians may wish to offer serologic testing for varicella susceptibility to history-negative adults who are likely to comply with return visits.

References

1. Meiklejohn G. Effectiveness of monovalent influenza A-prime vaccine during the 1957 influenza A-prime epidemic. Am J Hyg 1958;67:237-249.

2. Hoskins TW, Davies JR, Allchin A, et al. Controlled trial of inactivated influenza vaccine containing the A/Hong Kong strain during an outbreak of influenza due to the A/England/42/72 strain. Lancet 1973;ii:116-120.

3. Hammond ML, Ferris AA, Faine S, et al. Effective protection against influenza after vaccination with subunit vaccine. Med J Aust 1978;1:301-303.

4. Edmondson WP Jr, Rothenberg R, White PW, et al. A comparison of subcutaneous, nasal, and combined influenza vaccination. II. Protection against natural challenge. Am J Epidemiol 1971;93:480-486.

5. Edwards KM, Dupont WD, Westrich MK, et al. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. J Infect Dis 1994;169:68-76.

6. Weingarten S, Staniloff H, Ault M, et al. Do hospital employees benefit from the influenza vaccine? A placebo-controlled clinical trial. J Gen Intern Med 1988;3:32-37.

7. Austrian R. Surveillance of pneumococcal infection for field trials of polyvalent pneumococcal vaccines. Report DAB-VDP-12-84. Bethesda: National Institutes of Health, 1980.

8. Fine MJ, Smith MA, Carson CA, et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis of randomized controlled trials. Arch Intern Med 1994;154:2666-2677.

9. Kaufman P. Pneumonia in old age. Active immunization against pneumonia with pneumococcus polysaccharide: results of a six year study. Arch Intern Med 1947;79:518-531.

10. Klastersky J, Mommen P, Cantraine F, et al. Placebo controlled pneumococcal immunization in patients with bronchogenic carcinoma. Eur J Cancer Clin Oncol 1986;22:807-813.

11. Centers for Disease Control. Tetanus surveillance – United States, 1989-1990. MMWR 1992;41(SS-8):1-9.

12. Centers for Disease Control. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(RR-10):1-28.

13. Simonsen O, Bentzon MW, Kjeldsen K, et al. Evaluation of vaccination requirements to secure continuous antitoxin immunity to tetanus. Vaccine 1987;5:115-122.

14. Centers for Disease Control and Prevention. Measles – United States, 1994. MMWR 1995;44:486-487, 493-494.

15. Markowitz E, Preblud SR, Katz SL. Measles vaccine. In: Plotkin SA, Mortimer EA, ed. Vaccines. 2nd ed. Philadelphia:WB Saunders,1994.

16. Markowitz LE, Orenstein WA. Measles vaccine. Pediatr Clin North Am 1990;37:603-625.

17. Centers for Disease Control. Measles prevention: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1989;38(Suppl 9):1-18.

18. Szmuness W, Stevens CE, Harley EJ, et al. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 1980;303:833-841.

19. Andre FE. Overview of a 5-year clinical experience with a yeast-derived hepatitis B vaccine. Vaccine 1990;8(suppl):S74-S78.

20. Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection site, age, and smoking on the immune response to hepatitis B vaccination. Vaccine 1989;7:425-430.